The relationship between smoking and human health has been investigated mostly in
adults, despite the fact that the chemicals originating from sustained maternal smoking
disrupt the carefully orchestrated regulatory cascades in the developing fetus. In
this study, we followed molecular alterations in the umbilical cord (UC) vessels and
fetal red blood cells (RBCs), which faithfully reflect the in vivo status of the fetus.
We showed evidence for the decreased level of DNA-PKcs-positive nuclei in samples
with smoking origin, which is associated with the impaired DNA repair system. Furthermore,
we pointed out the altered ratio of MMP-9 metalloproteinase and its endogenous inhibitor
TIMP-1, which might be a possible explanation for the morphological abnormalities
in the UC vessels. The presented in vivo dataset emphasizes the higher vulnerability
of the veins, as the primary target for the toxic materials unfiltered by the placenta.
All these events become amplified by the functionally impaired fetal RBC population
via a crosstalk mechanism between the vessel endothelium and the circulating RBCs.
In our ex vivo approach, we looked for the molecular explanation of metal-exposure-induced
alterations, where expressions of the selected genes were upregulated in the control
group, while samples with smoking origin showed a lack of response, indicative of
prior long-term in utero exposure.
